Respiratory syncytial virus (RSV) is a single-stranded, negative sense RNA pleomorphic enveloped Pneumovirus of the Paramyxoviruidae family. Human RSV genome contains eight structural genes and two non-structural genes, wherein the major genes code for the attachment glycoprotein (G protein), the fusion protein (F protein), and a small hydrophobic envelope protein (SH protein), respectively.
The infection of RSV would lead to the induction of both humoral and cellular immune responses directed against the virus. It was proved in several studies in animal models that the RSV-specific neutralizing antibodies and cytotoxic lymphocytes (CTLs) contributed to a protection against RSV infection and/or diseases. For example, it was reported that RSV-specific antibodies played an important role in prevention from the RSV infection in terms of the protective efficacy of the passive transfer of immune sera containing RSV-specific antibodies of unvaccinated mice challenged by a live RSV (Graham et al., Immunoprophylaxis and immunotherapy of respiratory syncytial virus-infected mice with respiratory syncytial virus-specific immune serum; Pediatr Res 1993 August; 34(2):167-72). It was also reported that RSV-specific CTLs were detected more readily in adults who developed mild symptoms due to RSV infection exposure (Isaacs D., Viral subunit vaccines; Lancet 1991 May 18; 337(8751): 1223-4).
It was evidenced that F protein of RSV as target of vaccine antigen was better than G protein of RSV because the recombinant vaccinia virus expressing the G protein of RSV (vacvG) enhanced pulmonary eosinophilia upon RSV infection of mice (as reported in, for example, Openshaw et al., Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G; Int Immunol 1992 April; 4(4):493-500). However, it was also reported that Th-2 type response to RSV infection after F1-RSV-vaccination (a vaccination with the F1 subunit of F protein of RSV) played a role in an abnormal response, characterized by extensive eosinophils increasing in the blood, wheezing, and hyper reactive airways (Kim et al., Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine; Am J Epidemiol 1969 April; 89(4):422-34), and that the Th2-associated cytokines IL-4 and IL-13 both promoted the development of pulmonary eosinophilia (Johnson and Graham, Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism; J Virol 1999 October; 73(10):8485-95; and Johnson et al., IL-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge; J Immunol 2003 Feb. 15; 170(4):2037-45).
Given the above, it is still desired to develop a new vaccine for prevention against the RSV infection or the vaccine-enhanced diseases without undesired side effects, such as eosinophilia.